Sub theme 1.3
Degeneration and regeneration of tissues of the skeletal system


Goals of research: general outline
Scientific achievements
Future plans: special goals and approach
Running projects
Associated staff

Workgroup leaders   Department
dr.  P.M.  van  Hagen   Immunology
Prof. dr.ir.  M.  de  Jong   Nuclear Medicine
Prof.dr.  A.J.  van der  Lely   Internal Medicine
Prof. dr.  G.J.V.M.  van  Osch   Orthopaedics
Dr.  E.F.C.  van  Rossum   Internal Medicine
drs  A.  Umar   Medical Oncology

Goals of research: general outline

The skeletal system involves a number of connective tissues that together provide the shape and mechanical support of the human body. Aging or injury can affect these tissues and thereby hampering their function. This subtheme is concerned with the repair processes of deficient skeletal structures such as bone, cartilage or tendons. Tissue repair processes occur as a response to wounding, overloading or inflammation, but are often inappropriate and likely result in extra-cellular matrix of inferior quality. In specialized tissues, like e.g. articular cartilage, the latter contributes to progressive degeneration of the tissue.

Using a broad spectrum of multidisciplinary methods, our research projects aim to elucidate the mechanisms underlying normal physiological tissue turnover during homeostasis and processes that occur during degenerative skeletal diseases. In particular, we evaluate regenerative medicine options using tissue engineering or cell therapeutic approaches. In vitro, we are aiming to differentiate skeletal (progenitor) cells towards certain phenotypes to achieve the wanted tissue properties like e.g. the mechanically robust tissue architecture and matrix properties characteristic for articular cartilage. In addition, novel molecular targets form our basis to seek new therapeutic treatment options. In preclinical animal testing our in-vitro concepts are being tested and evaluated using novel in-vivo imaging techniques. The preclinical experiments are translated in clinical research that aims for new orthopedic regenerative intervention strategies.


Scientific achievements

Development and evaluation of imaging methods with micro-CT and micro-SPECT for in-vivo follow up of bone architecture and turnover, cartilage changes and macrophage activity in animal models for osteoporosis and osteoarthritis.

In different animal models the relation between subchondral bone response and cartilage damage after induction of osteoarthritis is investigated. Indications for interaction between the cartilage and the subchondral bone compartment are found.

Glucosamine is demonstrated to have effects on the metabolism of chondrocytes using cell and tissue culture experiments. In a clinical trial glucosamines were not effective.

Changes in tissue metabolism and composition during tendinopathies have been described and several models and analytical tools to perform translational tendon research are introduced in the group.

The effects of several growth factors (FGF-2, IGF-1, TGF-beta) and extracellular matrix components (COMP, collagen IX, glycosaminoglycans) on collagen assembly by chondrocytes and function of the newly formed matrix were studied.

Bone density and shape is being analysed in detail in both animal models and patients, using sophisticated pattern recognition models that correlate with and might predict bone and joint diseases such as osteporosis and osteoarthritis.


Future plans: special goals and approach

Modulating chondrogenesis using growth factors or pharmaceutical intervention: knowledge of embryonic development can be used to optimize culture media supplementation with e.g. growth factors or cell signaling modulators in order to control cellular phenotype and favor proper tissue formation.

Cartilage repair studies: cytokines, growth factors and/or bioactive molecular compounds that can be released by (custom-tailored) biomaterials or bone marrow derived stromal cells. The aim is to understand how certain secretable factors can be used to modulate tissue turnover in order to prevent degradation and/or stimulate regeneration.

(Molecular) skeletal imaging: imaging methods enabling us to follow bone and cartilage changes in small animal models will be used to evaluate new interventions for osteoporosis, osteoarthritis or implant fixation. In addition, special methods for cell tracking will be employed such as super-paramagnetic iron oxide labeling using MRI or heterogenic reporter gene expression using ultra-sensitive SPECT tracing.

Clinical skeletal imaging: the development of osteoarthritis will be studied using different imaging modalities in (large) cohort studies in combination with novel image analyses that enable to accurately quantify cartilage changes, bone changes and disease development. In addition, the relation between bone shape and genetics (polymorphisms) will be studied.


Most recent publications

1.      Uitterlinden EJ, Jahr H, Koevoet JL, Jenniskens YM, Bierma-Zeinstra SM, Degroot J, Verhaar JA, Weinans H, van Osch GJ. Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants. Osteoarthritis Cartilage. 2006 Mar;14(3):250-7. IF: 4.0; 1/43 (Orthopedics)

2.      Jenniskens YM, Koevoet JL, de Bart ACW, Weinans H, Jahr H, Verhaar JAN, De Groot J, van Osch GJVM. Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFbeta2 and FGF2. Osteoarthritis and Cartilage. 2006; Nov;14(11):1136-46 IF: 4.0; 1/43 (Orthopedics)

3.      Waarsing, JH, Day, JS, Verhaar, JAN, Ederveen, AGH, Weinans, H. Bone loss dynamics result in trabecular alignment in aging and ovariectomized rats. J. Orthop. Res. 24:926-935, 2006. IF: 2.8; 2/43 (Orthopedics)

4.      de Mos M, van El B, Degroot J, Jahr H, van Schie HT, van Arkel ER, Tol H, Heijboer R, van Osch GJ, Verhaar JA.  Achilles Tendinosis: Changes in Biochemical Composition and Collagen Turnover Rate. Am J Sports Med.  2007 Sep;35(9):1549-56  IF 3.3, 2/48 (Orthopedics)

5.      Gregory JS, Waarsing JH, Day J, Pols HA, Reijman M, Weinans H, Aspden RM. Early identification of radiographic osteoarthritis of the hip using an active shape model to quantify changes in bone morphometric features: can hip shape tell us anything about the progression of osteoarthritis? Arthritis Rheum. 56:3634-43, 2007. IF: 7.7; 1/22 (Rheumatology)

6.      Botter SM, van Osch GJ, Waarsing JH, van der Linden JC, Verhaar JA, Pols HA, van Leeuwen JP, Weinans H. Cartilage damage pattern in relation to subchondral plate thickness in a collagenase-induced model of osteoarthritis. Osteoarthritis Cartilage 16:506-14, 2008.  IF: 4.1; 1/49 (Orthopedics)

7.      Bastiaansen-Jenniskens YM, Koevoet W, de Bart AE, Zuurmond A-M, Bank RA; Verhaar JAN, DeGroot J, van Osch GJVM. TGF-beta affects collagen cross-linking independent of chondrocyte phenotype but strongly depending on physical environment. Tissue Engineering, Tissue Eng Part A. 2008 Jun;14(6):1059-66 IF 4.6, 13/144 (Biotech & applied Microbiology)

8.      Piscaer TM, Waarsing JH, Kops N, Pavljasevic P, Verhaar JA, van Osch GJ, Weinans H. In vivo imaging of cartilage degeneration using microCT-arthrography. Osteoarthritis Cartilage. 16:1011-7, 2008.  IF: 4.1; 1/49 (Orthopedics)

9.      Botter SM, Glasson SS, Hopkins B, Clockaerts S, Weinans H, van Leeuwen JP, van Osch GJ. ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes. Osteoarthritis Cartilage. 2009 May; 17(5): 636-645. IF 4.0, 1/49 (Orthopedics)

10.  Rozendaal RM, Koes BW, van Osch GJ, Uitterlinden EJ, Garling EH, Willemsen SP, Ginai AZ, Verhaar JA, Weinans H, Bierma-Zeinstra SM. Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial. Ann Intern Med. 2008 Feb 19;148(4):268-77. IF 16.1, 4/107 (Medicine, General & Internal)


People associated with sub theme 1.3: Degeneration and regeneration of tissues of the skeletal system
Name Position Department
Dr.  E.  Ahmad PhD-candidate Endocrinology
H.  Alves Postdoc/junior researcher Rheumatology
EAS  Andres Sastre PhD-candidate Orthopaedics
prof.dr.  J.N.  van den  Anker
ли&  Paulpeter  Arthursap Postdoc/junior researcher General Surgery
dr  W.H.  Bakker Senior researcher not being a workgroup leader Nuclear Medicine
W.  Beumer Other as mentioned (please specify in remarks) Immunology
MD  A.S.  de  Boer PhD-candidate Surgery
Dr.  J.A.M.  Braks Senior researcher not being a workgroup leader Maxillofacial Surgery
Dr.  W.A.P.  Breeman Senior researcher not being a workgroup leader Nuclear Medicine
Dr.  A.O.  Brinkmann Assistent professor (UD) Endocrinology
F.  Broglio PhD-candidate Endocrinology
drs.  M.P.  Brugts PhD-candidate Endocrinology
drs.  C.  de  Bruin PhD-candidate Endocrinology
MSc  A.M.  Brum PhD-candidate Internal Medicine
drs.  E.  Bultman PhD-candidate Endocrinology
R.J.  Burer PhD-candidate Orthopaedics
S.C.  Capar PhD-candidate Orthopaedics
Dr.  G.T.G.  Chang Assistent professor (UD) Endocrinology
Msc  M.A.  Cleary PhD-candidate Orthopaedics
Dr.  R.  Croxen Senior researcher not being a workgroup leader Endocrinology
MD  MC  De Martino Postdoc/junior researcher Internal Medicine
A.  Dehghan Senior researcher not being a workgroup leader Epidemiology
drs.  M.J.H.J.  Dekker PhD-candidate Endocrinology
dr  P.J.D.  Delhanty Senior researcher not being a workgroup leader Internal Medicine
MD  N.D.  Direk PhD-candidate Epidemiology
Tmmaverick  Elmerdig PhD-candidate General Surgery
S.  Fahmy Garcia PhD-candidate Orthopaedics
N.F  Fahy Postdoc/junior researcher Orthopaedics
dr  R.A.  Feelders Senior researcher not being a workgroup leader
MSc  M  Ferrao Blanco PhD-candidate Orthopaedics
Drs.  J.  Gaal PhD-candidate Pathology
C.  Gauna PhD-candidate Endocrinology
drs.  M.T.  de  Graaf PhD-candidate Neuro Oncology
Drs  L.C.G.  de  Graaff PhD-candidate Internal Medicine
D.D.  Grancharova PhD-candidate CODT
Drs  N.  Grotenhuis PhD-candidate Surgery
MSc  M.F.P.  de  Haas PhD-candidate Orthopaedics
dr.  P.M.  van  Hagen Workgroup leader within the School Immunology
dr.  W.W.  de  Herder Senior researcher not being a workgroup leader Internal Medicine
E.G.  van den  Herik PhD-candidate Neurology
drs.  J.  Hofland PhD-candidate Endocrinology
Drs.  W.A.  den  Hollander-Huijsman PhD-candidate Endocrinology
Drs.  N.  Jafari PhD-candidate Neurology
P.M.  Jansen PhD-candidate Internal Medicine
dr.  J.A.M.J.L.  Janssen Senior researcher not being a workgroup leader Neurology
Prof. dr.ir.  M.  de  Jong Workgroup leader within the School Nuclear Medicine
drs  EM  de  Jong PhD-candidate Clinical Genetics
MD, MSc  A.H.C.  de  Jongste PhD-candidate Neurology
MSc  Y.S.  Kap PhD-candidate Immunology
Drs.  P.M.J.H.  Kemperman PhD-candidate Dermatology
I.A.  Ketelslegers Physician (MD) Neurology
S.  Khan PhD-candidate Nuclear Medicine
MD  S.  Khatab PhD-candidate Orthopaedics
P.M.  van  Koetsveld Senior researcher not being a workgroup leader Endocrinology
P.P.M.  Kooij Senior researcher not being a workgroup leader Nuclear Medicine
dr.  F.J.W.  Koper Senior researcher not being a workgroup leader Internal Medicine
PhD  E.K.  Korpershoek PhD-candidate Pathology
Drs., MSc  K.L.  Kreft PhD-candidate Neurology
prof.dr.  E.P.  Krenning Workgroup leader within the School Nuclear Medicine
Dr.  R.R.  de  Krijger Senior researcher not being a workgroup leader Pathology
Dr.  JJCM  Kruse Other as mentioned (please specify in remarks) Research and Development
Dr.  JJCM  Kruse Other as mentioned (please specify in remarks) Research and Development
Dr.  R.W.  Kuijpers Senior researcher not being a workgroup leader
dr.  D.J.  Kwekkeboom Senior researcher not being a workgroup leader Nuclear Medicine
drs  DM  van de  Laarschot PhD-candidate Endocrinology
T.M.J.  de  Laat Other as mentioned (please specify in remarks) Internal Medicine
Prof.dr.  S.W.J.  Lamberts Senior researcher not being a workgroup leader Endocrinology
J  Lehmann PhD-candidate Otorhinolaryngology and head and neck surgery
Drs.  M.J.C.  Leijs PhD-candidate Orthopaedics
Prof.dr.  A.J.  van der  Lely Workgroup leader within the School Internal Medicine
Dr.  AL  Lolli Postdoc/junior researcher Orthopaedics
Dr.  P.J.  Lugtenburg Postdoc/junior researcher
Smooveb73  Maximjnc Senior researcher not being a workgroup leader General Surgery
Drs  M.  Medici PhD-candidate Endocrinology
R.L.  Miclea PhD-candidate Pediatrics Endocrinology
Ms  Z.D.  Mumcuoglu Guvenc PhD-candidate Orthopaedics
B.A.  Naaijkens Postdoc/junior researcher Orthopaedics
R.N.  Narcisi Postdoc/junior researcher Orthopaedics
YN  Nossin PhD-candidate Otorhinolaryngology and head and neck surgery
Prof. dr.  G.J.V.M.  van  Osch Workgroup leader within the School Orthopaedics
V.  Palomares Cabeza PhD-candidate Otorhinolaryngology and head and neck surgery
Drs.  R.P.  van der   Pas PhD-candidate Internal Medicine
Drs.  B.J.  Petri PhD-candidate Pathology
M.M.  Pleumeekers PhD-candidate Surgery
Ing  A.  van der   Ploeg Technician CODT
S.  Potikanond PhD-candidate Molecular Biology
Drs.  M.  van  Putten PhD-candidate Humane Genetics
R.A.M.  Quax PhD-candidate Endocrinology
Dump pin shop  Tmmaverick  RobertIcect Senior researcher not being a workgroup leader General Surgery
Dr.  E.F.C.  van  Rossum Workgroup leader within the School Internal Medicine
drs.  T.F.  Runia Physician (MD) Neurology
drs  H.  Russcher PhD-candidate Internal Medicine
Dr.  A.M.  Samara Postdoc/junior researcher Endocrinology
Drs.  M.J.  Sandker PhD-candidate Orthopaedics
E.  van  Schaik PhD-candidate Immunology
-  Tmmaverick  SEOmab PhD-candidate General Surgery
PhD  K  Sivasubramaniyan Assistent professor (UD) Orthopaedics
Drs.  I.M.  van der  Sluis None Endocrinology
dr.  P.  Smit PhD-candidate Internal Medicine
Drs.  J.  van der  Stok PhD-candidate Orthopaedics
P.  Sukho PhD-candidate Otorhinolaryngology and head and neck surgery
0day Music For DJs  Paulpeter  TerryfUnny MSc student (please specify in remarks) General Surgery
ir  E.  Teuling PhD-candidate Neuroscience
drs.  J.  Teunissen PhD-candidate Nuclear Medicine
dr.  H.B.  Thio Senior researcher not being a workgroup leader Dermatology
drs  A.  Umar Workgroup leader within the School Medical Oncology
MSc  L.  Utomo PhD-candidate Orthopaedics
Dr.  R.  Valkema Senior researcher not being a workgroup leader Nuclear Medicine
Drs.  A.J.  Varewijck PhD-candidate Endocrinology
drs  M.  van der  Velde PhD-candidate Endocrinology
W.P.  Vermeij Postdoc/junior researcher Genetics
MD  G.  Vitale Senior researcher not being a workgroup leader Endocrinology
New Project  Boogieq  vivianak4 MSc student (please specify in remarks) General Surgery
Drs.  E.I.  van  Vliet PhD-candidate Nuclear Medicine
C  Voskamp PhD-candidate Orthopaedics
Drs.  J.M.  de  Vries PhD-candidate Neurology
A.M.  Waaijers Technician Internal Medicine
W.J.  de  Waal
C.  Walgaard Physician (MD) Neurology
Drs.  K.  van der   Weerd PhD-candidate Immunology
Drs.  W.  Wei PhD-candidate Orthopaedics
S.F.H.  De   Witte MSc student (please specify in remarks) Orthopaedics
MD  J.L.  Yin PhD-candidate Internal Medicine
Drs.  E.P.M.  van der   Zanden PhD-candidate Gastro-enterology and Hepatology
Ir. Dr.  M.  van  Zwam PhD-candidate